Neuromonitoring is a subfield of clinical patient monitoring focused on measuring various aspects of brain function and on changes therein caused by drugs commonly used to induce and maintain anesthesia in an operation room or sedation in patients under critical or intensive care.
Electroencephalography (EEG) is a well-established method for assessing brain activity by recording and analyzing the weak biopotential signals generated in the cortex of the brain with electrodes attached on the skin of the skull surface. The EEG has been in wide use for decades in basic research of the neural systems of the brain, as well as in clinical diagnosis of various neurophysiological diseases and disorders.
One field of application for EEG measurement is sleep analysis. Various EEG-based methods have been designed for automated sleep classification, for example, which allow sleep to be divided into different stages according to its depth.
The autonomic nervous system (ANS) is the ‘unconscious’ nervous system, which controls and regulates virtually all of our basic body functions, such as cardiac function, blood circulation and glandural secretion. The main parts of the ANS are the parasympathetical and sympathetical nervous branches. The sympathetic nervous system (SNS) usually prepares us for high stress situations by speeding up the body functions. Under conditions of normal ANS regulation, the parasympathetic system restores the normal conditions in blood circulation by slowing down the heart rate. Pain and discomfort, for example, may activate the SNS and cause an increase in blood pressure, heart rate, and adrenal secretions.
Heart rate variability (HRV) has traditionally been used as a surrogate measure of autonomic activation. Low frequency (LF) components of an HRV signal correspond to both sympathetic and parasympathetic activity, while higher frequency (HF) components correspond to parasympathetic activity only. Thus, the ratio of the LF components to the HF components (LF/HF), so-called sympatho-vagal ratio, can be used to quantify the level of sympathetic activation.
Various parameters indicative of the activity of the ANS or SNS have also been utilized in sleep analysis. U.S. Pat. No. 5,280,791, for example, discloses a method for separating REM sleep and non-REM sleep based on HRV variables derived from an ECG signal. U.S. Pat. No. 6,319,205 in turn discloses a method for detecting REM sleep by measuring peripheral arterial tone. In this method, a static pressure field is applied around the distal part of a digit of a subject and changes in the peripheral arterial tone are monitored.
Generally, anesthetic agents affect the functioning of the autonomic nervous system. Anesthetics mainly depress autonomic activity, which can be seen, for example, as dropping of the blood pressure and depression of the total HRV power. Propofol, for example, which is a rather pure hypnotic drug, has been reported to reduce both sympathetic and parasympathetic tone. Midazolam in turn is associated with lowered LF and HF powers as compared to baseline levels, while dexmedetomidine decreases sympathetic tone with attenuation of hemodynamic responses to anesthesia and surgery. Similar effects are observed with the smaller doses associated with sedation.
Drug-induced unconsciousness and natural sleep produce EEG patterns that are quite similar to each other. The discrimination of these states based on the EEG signal is therefore impossible with current methods, at least in short time windows of a few minutes. Dexmedetomidine, for example, has attracted attention as a sedative agent due to its ability to induce a state which is quite similar to non-REM sleep. The EEG patterns measured under the influence of sedative/anesthetic drugs (e.g. dexmedetomidine, propofol and midazolam) and during natural sleep are very much alike.
Due to the EEG resemblances, the current sleep monitoring methods are incapable of separating drug-induced unconsciousness from natural sleep. However, such an ability would provide clinicians extra information in various situations in which a patient appears to be in sleep but it is not clear whether the state of unconsciousness is caused by drugs or natural sleep.
The present invention seeks to eliminate the above drawback and to accomplish a mechanism capable of separating drug-induced unconsciousness from natural sleep.